Successful treatment of early stage cancer, such as prostate and breast cancer, depends on completely resecting all disease, while sparing normal tissue. Consequently, the surgeon is faced with a difficult clinical decision: remove an additional margin of healthy appearing tissue, risking additional morbidity or risk leaving microscopic disease behind. Microscopic residual disease (MRD) leads to increased local recurrence (LR) and, potentially, reduced overall survival (OS). Therefore patients are often subjected to additional treatment (such as re-resection, radiation, and/or chemotherapy) to reduce the chance of recurrence; a result that could have been avoided if the entire tumor was initially removed. Although crude methods exist to evaluate tumor in the operating room, definitive identification of MRD can only be determined days later after molecular staining and microscopic visualization of the excised specimen in a pathology laboratory, rendering it ineffective for intraoperative guidance.
Identification of MRD is a prime concern in almost every oncological case. The device presented here is meant to be a platform imager for use with any disease subsite where surgical resection is necessary for cure, and for which there is a targeted agent capable of labeling and identifying the cancer cell. One example is breast cancer, whereby microscopic tumor is left in the tumor bed in one out of four operations. Microscopic residual disease doubles the rate of recurrence and thereby decreases overall survival. Therefore a repeat operation is essential. This could have avoided if all disease was resected during the initial operation. Another example is in prostate cancer, where a positive margin (another term for microscopic residual disease) increases the chance of cancer recurrence. Due to the morbidity of reoperation, patients with MRD are advised to receive post-operative radiotherapy, lasting approximately 6 weeks with significant cost and additional side effects. These are just a few examples of tumors types whereby leaving disease behind results in poorer oncologic outcomes or necessitates additional treatment. Therefore, there is a strong need to intraoperative identify MRD within the tumor bed to guide complete resection in a single surgery preventing both the morbidity and cost associated with multiple therapeutic procedures.
Although methods of intraoperative imaging for tumor tissue exist, these implementations are microscopes restricted to line-of-sight imaging far from the tumor bed due to their bulky size and rigid optics, preventing visualization of the majority of the tumor bed and resulting in poor sensitivity since the optical signal from the fluorophore deteriorates as the distance-squared. Fiber-optic approaches are not flexible enough to visualize small complex tumor cavities, and have too small a visual field to effectively visualize the entire tumor bed. Therefore, the device described in this patent solves these problems by employing a novel approach of placing the imaging sensor directly on the tumor bed surface, increasing sensitivity. To obtain cellular level resolution, combined with the ability to maneuver within the tumor bed, small fluorescent microscopes (on the order of a 100 microns) are patterned in a large array. This enables each microscope-element to visualize a population of roughly 100-200 cells, while the entire array operates in parallel, effectively imaging the entire tumor bed rapidly.